title: Leptin modulates enteric neurotransmission in the rat proximal colon: an in vitro study.
abstract: Leptin has been shown to modulate gastrointestinal functions including nutrient absorption, growth, and inflammation and to display complex effects on gut motility. Leptin receptors have also been identified within the enteric nervous system (ENS), which plays a crucial role in digestive functions. Although leptin has recently been shown to activate neurons in the ENS, the precise mechanisms involved are so far unknown. Therefore, the aim of the present study was to determine the effects of leptin on rat proximal colon smooth muscle and enteric neuron activities. The effects of exogenous leptin on tone and on responses to transmural nerve stimulation (TNS) of isolated circular smooth muscle of proximal colon in rats were investigated using an organ bath technique. The effects of a physiological concentration (0.1 μM) of leptin were also studied on tone and TNS-induced relaxation in the presence of atropine, hexamethonium, L-N(G)-nitroarginine methyl ester (L-NAME) and capsazepine. Leptin caused a slight but significant decrease in tone, TNS-induced relaxation and contraction in a concentration-dependent manner in colonic preparations. Cholinergic antagonists abolished the effects of 0.1 μM leptin on TNS-induced relaxation. This concentration of leptin had no further effect on relaxation in the presence of L-NAME. In the presence of capsazepine, leptin had no further effect either on tone or relaxation compared to the drug alone. In conclusion, leptin modulates the activity of enteric inhibitory and excitatory neurons in proximal colon. These effects may be mediated through nitrergic neurons. Intrinsic primary afferent neurons may be involved.
authors.affiliation: Université de Strasbourg, Institut Pluridisciplinaire Hubert Curien, 23 rue Becquerel, 67087 Strasbourg, France; CNRS, UMR7178, 67037 Strasbourg, France.
authors.forename: Voinot
authors.initials: V
authors.lastname: Florian
authors.forename: Fischer
authors.initials: F
authors.lastname: Caroline
authors.forename: Crenner
authors.initials: C
authors.lastname: Francis
authors.forename: Schmidt
authors.initials: S
authors.lastname: Camille
authors.forename: Angel
authors.initials: A
authors.lastname: Fabielle
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D017615:Enteric Nervous System / Q000502:physiology; D018738:Hexamethonium / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission
chemical_list: D018679:Cholinergic Agonists; D020738:Leptin; D018733:Nicotinic Antagonists; D009569:Nitric Oxide; D018738:Hexamethonium; D019001:Nitric Oxide Synthase; C071423:capsazepine; D000109:Acetylcholine; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester
keywords: ACh; Adipokines; C; CCK; CMPC; Cholinergic neurons; ENS; Enteric nervous system; GI; Gut; IPANs; L-NAME; L-NG-nitroarginine methyl ester; NO; NOS; Nitrergic neurons; R; TNS; acetylcholine; cholecystokinin; circular muscle from proximal colon; contraction; enteric nervous system; gastrointestinal; intrinsic primary afferent neurons; nitric oxide; nitric oxide synthase; relaxation; transmural nerve stimulation